Edaravone alleviates brain-to-heart signaling after ischemia and reperfusion injury in aged rats

Aims: The present study was to reveal the molecular mechanism of the protective effect of edaravone, a novel drug with antioxidant properties, against oxidative damage in brain-to-heart signaling triggered by ischemia-reperfusion (I/R) injury to the brain by using an animal model of bilateral carotid artery occlusion (BCAO). Methods: Male Sprague-Dawley rats were divided into sham group, vehicle group, and edaravone group. Rat model of BCAO was constructed. Glutathione peroxidase (GSHPx) activity was determined. Enzyme-linked immunosorbent assay was used to determine the level of protein carbonyl. Western blotting was performed to measure inducible nitric oxide synthase (iNOS) level. Terminal deoxynucleotidyl transferase nick end labeling (TUNEL) assay was performed to study histopathologic damages. Results: In the brain, reperfusion decreased the level of GSHPx and significantly increased protein carbonyl level, iNOS level and the percentage of TUNEL-positive nuclei. Expression of iNOS that was decreased after drug treatment was accompanied with a decrease in the percentage of TUNEL-positive nuclei. c-Jun N-terminal kinase (JNK) activity was significantly correlated with the percentage of TUNEL-positive nuclei. In the heart, no significant change in the activity of GSHPx was observed. However, there was a mild decrease in protein carbonyl level and increase in iNOS expression. Mitogen-activated protein kinase (MAPK) activity in the heart was different from that in brain tissue, with significant activation of p38 MAPK. These results were further complimented by a slight increase in the percentage of TUNEL-positive cells in heart sections. The above-mentioned events were reversed by treatment with edaravone (3 mg/kg, i.v.). Conclusion: The present study demonstrates that edaravone ameliorates oxidative damage in brain-to-heart signaling after cerebral ischemia-reperfusion injury by modulating MAPK activity and normalizing oxidative stress in aged rats.